Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently identified a new exon of the CD44 gene and demonstrated abnormal retention of a noncoding section, intron 9, in mRNA from bladder carcinomas. To analyze this further, the present study examined CD44 gene expression in cell lines from 14 esophageal, 3 colonic, and 4 breast carcinomas and in fresh samples from 20 colorectal carcinomas and corresponding normal colonic mucosa, using reverse transcriptase followed by the polymerase chain reaction (RT-PCR). This confirmed that there was abnormal assembly of several exons of the gene in cell lines and in tumor tissues from these organs. However, the most striking new finding was that intron 9 was present in RNA from 11 esophageal, 3 colon, and 1 breast carcinoma cell line, respectively. This was confirmed by RNase and DNase digestion analysis. Moreover, it was detected both in nuclear and cytoplasmic mRNA fractions, indicating that abnormal splicing of pre-mRNA occurs in cancer cells. The abnormal retention of intron 9 in CD44 gene transcripts was also demonstrated in tumor tissues from 16 (80%) of 20 patients with colon carcinoma, but there was no correlation with Dukes' stage. The biological significance of these observations is not yet understood. However, it is clear that, as with the abnormal expression pattern of CD44 variant exons, intron 9 retention is a good-candidate molecular diagnostic tool for colorectal carcinomas.
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PMID:Abnormal retention of intron 9 in CD44 gene transcripts in human gastrointestinal tumors. 754 38

The protein tyrosine phosphatase alpha (PTP alpha) mRNA level in paired samples of late stage (Dukes' D) colorectal tumors and adjacent normal colon mucosa was quantified by RNase protection assays. After normalization against 18S RNA or beta-actin mRNA level, a 2-10-fold increase in PTP alpha mRNA was detected in 10 of 14 tumors (approximately 70%) compared to mucosa. In situ hybridization of digoxigenin-labelled antisense PTP alpha RNA to tumor and mucosa sections produced a signal only in neoplastic cells of the tumor sample, consistent with the high increase in PTP alpha mRNA detected by RNase protection assays of some of the tumors. This is the first report suggesting an association of a protein tyrosine phosphatase with colorectal carcinoma. PTP alpha is a receptor-like PTP thought to be involved in regulating cell proliferation. Its oncogenic properties when overexpressed in cultured fibroblasts suggest that PTP alpha overexpression could contribute to the tumorigenic process in colon carcinoma.
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PMID:Increased mRNA expression of the receptor-like protein tyrosine phosphatase alpha in late stage colon carcinomas. 762 35

The identification of novel autocrine/paracrine signaling pathways and possible markers represents an important component in the understanding of tumor growth control. In this study, we assessed the potential role of insulin-like growth factor-I (IGF-I), the IGF-I receptor (IGF-IR) and IGF binding protein-2 (IGFBP-2) in human colorectal cancer. Initial studies demonstrating increased IGF-I binding and IGF-IR density in human colon cancer tissue revealed that a component of iodinated (3-[125-I]iodotyrosyl) IGF-I (125I-ICGF-I) binding was not attributable to IGF-IR. Binding studies and Western blot analysis suggested that this second component of 125I-IGF-I binding could be due to IGFBP-2. Further analysis by a specific solution hybridization/RNase protection assay for IGF-IR mRNA levels, IGFBP-2 mRNA levels and in situ hybridization for IGFBP-2 localization, was carried out in nine patients with colon cancer. IGF-IR mRNA levels by RNAse protection assays were unchanged, whereas IGFBP-2 mRNA levels were increased 4-8-fold in patients with colon cancer compared to controls. Three patients with Dukes stage C disease had the highest levels of IGFBP-2 mRNA. In situ hybridization studies localized IGFBP-2 mRNA to malignant cells and not to the surrounding stromal cells, suggesting an autocrine role for IGFBP-2. The discrepancy between increased IGF-I binding, IGF-IR density, IGFBP-2 mRNA and the minimal modulation of the IGF-IR mRNA implies post-transcriptional regulation of IGF-IRs. Our results suggest that IGFBP-2 may be implicated in colon cancer metastases and prognosis. Its usefulness as a potential tumor marker should be further investigated.
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PMID:Role of insulin-like growth factor-I (IGF-I) receptor, IGF-I, and IGF binding protein-2 in human colorectal cancers. 1098 59

The cytoplasmic ribonuclease DICER1 is one of the key enzymes in microRNA (miRNA) processing, essential for the production of mature miRNA. The effect of DICER1 expression in tumor cells on the prognosis of patients with several cancers has been examined with controversial results in various cancer types. In particular, the clinical significance of DICER1 expression in colorectal cancer (CRC) patients has yet to be determined. The aim of this study was to evaluate the correlation between the DICER1 mRNA levels and the clinicopathological characteristics and prognostic significance in CRC patients. Tumor and normal adjacent tumor tissues from 260 patients with CRC (Dukes' stage A: 40 cases, Dukes' B: 68 cases, Dukes' C: 88 cases and Dukes' D: 64 cases) were examined. The DICER1 mRNA levels were measured using the TaqMan real-time reverse transcription polymerase chain reaction (RT-PCR) method. The expression levels of DICER1 mRNAs showed a significant decrease in CRC tissues as compared to normal ones (P=0.039). A statistically significant association was observed between DICER1 mRNA expression and tumor size, depth of invasion, lymph node metastasis, lymphatic invasion and Dukes' stage. In Kaplan-Meier survival curve analysis, overall survival (OS) and disease-free survival (DFS) rates of patients with a low DICER1 mRNA expression were significantly worse compared to patients with a high DICER1 mRNA expression (OS P<0.001; DFS P<0.001). In the Cox multivariate analysis, DICER1 mRNA expression in CRC tissues was identified as an independent prognostic factor for OS [hazard ratio (HR), 0.30; 95% confidence interval (CI), 0.13-0.64; P=0.001] and DFS (HR, 0.23; 95% CI, 0.10-0.48; P=0.001). This study demonstrated that a reduced DICER1 mRNA expression is associated with poor prognosis in CRC patients.
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PMID:Clinicopathological and prognostic significance of the microRNA processing enzyme DICER1 mRNA expression in colorectal cancer patients. 2464 59